A Novel Mutation of Mitochondrial T14709C Causes Myoclonic Epilepsy with Ragged Red Fibers Syndrome in a Chinese Patient / 中华医学杂志(英文版)

<p><b>Background</b>Myoclonic epilepsy with ragged red fibers (MERRF) syndrome is characterized by myoclonus, generalized epilepsy, cerebellar ataxia, and ragged red fibers (RRFs) in the muscle. T-to-C transition at nucleotide position 14709 in the mitochondrial tRNA glutamic acid (tRNA) gene has previously been associated with maternally inherited diabetes and deafness. However, the association between MERRF and mitochondrial T14709C mutation (m.T14709C) has never been reported before.</p><p><b>Methods</b>Clinical information of a 17-year-old patient was collected; muscle biopsy and next-generation sequencing (NGS) of whole mitochondrial and neuromuscular disease panel were then conducted. Finally, sanger sequencing was carried out to confirm the mutations.</p><p><b>Results</b>The patient presented a typical MERRF phenotype with muscle weakness, epileptic seizure, clonic episodes, cerebellar ataxia, and spinal scoliosis. Muscle biopsy showed RRFs which indicated abnormal mitochondrial functions. NGS of whole mitochondrial gene revealed m.T14709C mutation, confirmed by Sanger sequencing.</p><p><b>Conclusion</b>We present a sporadic patient with typical MERRF presentation carrying the mutation of m.T14709C, which expanded the spectrum of m.T14709C.</p>

Research progress and literature review of animal models of osteoporosis / 中国组织工程研究

BACKGROUND: Osteoporosis, known as "a quiet epidemic disease", is an "invisible killer" that impairs the health of the elderly. Fracture as the most dangerous complication of osteoporosis is not only a medical problem, but also a serious social problem. OBJECTIVE: To summarize the selection, establishment methods, characters and evaluation of the animal model of osteoporosis. METHODS: A computed-based search of CBM, WanFang, VIP, CNKI and PubMed databases was conducted for the relevant articles published from January 1986 to December 2016 using the keywords of "osteoporosis, animal models" in English and Chinese, respectively. Finally 39 articles were included for result analysis after reading the title and abstract. RESULTS AND CONCLUSION: Animal experiments play an important role in the studies of osteoporosis, so a desirable animal model should hold similarity, reliability, repeatability, applicability, controllability, efficacy and economy. Osteoporosis is a progressive and long-lasting disease that has different characteristics at different stages. But an animal model only simulates one etiology, one stage, major symptoms and pathophysiological changes, and cannot exhibit the whole pathological changes. The current study suggests that animal species and modeling methods can affect the characters of models, and there is a lack of standards for animal age, feeding methods, modeling time and assessment.

Identification of Seven Novel Mutations in the Acid Alpha-glucosidase Gene in Five Chinese Patients with Late-onset Pompe Disease / 中华医学杂志(英文版)

<p><b>Background</b>Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene (GAA). A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease (LOPD) who carried novel GAA gene mutations.</p><p><b>Methods</b>Clinical and pathological data of patients diagnosed with glycogen storage disease at our institution from April 1986 to August 2017 were collected, and next-generation sequencing of frozen muscle specimens was conducted.</p><p><b>Results</b>Of the five patients included in the study, the median disease onset age was 13 years, with a median 5 years delay in diagnosis. The patients mainly manifested as progressive weakness in the proximal and axial muscles, while one patient developed respiratory insufficiency that required artificial ventilation. In muscle biopsies, vacuoles with variable sizes and shapes appeared inside muscle fibers, and they stained positive for both periodic acid-Schiff and acid phosphatase staining. Ten GAA gene mutations, including seven novel ones (c.796C>A, c.1057C>T, c.1201C>A, c.1780C>T, c.1799G>C, c.2051C>A, c.2235dupG), were identified by genetic tests.</p><p><b>Conclusions</b>The seven novel GAA gene mutations revealed in this study broaden the genetic spectrum of LOPD and highlight the genetic heterogeneity in Chinese LOPD patients.</p>

A patient with myofibrillar myopathy caused by BAG3 gene mutation / 中华神经科杂志

Objective To study the clinical,pathological and genetic features of myofibrillar myopathy caused by BAG3 gene mutation.Methods The clinical features and pathological findings of a patient with myofibrillar myopathy were analyzed.Genomic DNA of the patient was extracted from peripheral blood and the next generation sequencing was performed to explore the mutation of genes about myopathies.Results The patient presented with nine-year-old onset myopathy characterized by progressive difficulty for squatting,rigid spine and muscle atrophy in the limbs symmetrically.Peripheral neurogenic damages were found on electromyography.On muscle biopsy,myogenic and neurogenic damages with rimmed vacuoles appeared,and the deposited materials were positive for sarcoglycan,dystrophin-R and dystrophin-C.There was a reported heterozygous mutation in the exons of the BAG3 gene (c.626C ＞ T).Conclusion There is no specificity of clinical manifestation in myofibrillar myopathy,and the diagnosis of this disease mainly depends on muscle biopsy and genetic screening.

Oculopharyngeal Weakness, Hypophrenia, Deafness, and Impaired Vision: A Novel Autosomal Dominant Myopathy with Rimmed Vacuoles / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Myopathies with rimmed vacuoles are a heterogeneous group of muscle disorders with progressive muscle weakness and varied clinical manifestations but similar features in muscle biopsies. Here, we describe a novel autosomal dominant myopathy with rimmed vacuoles in a large family with 11 patients of three generations affected.</p><p><b>METHODS</b>A clinical study including family history, obstetric, pediatric, and development history was recorded. Clinical examinations including physical examination, electromyography (EMG), serum creatine kinase (CK), bone X-rays, and brain magnetic resonance imaging (MRI) were performed in this family. Open muscle biopsies were performed on the proband and his mother. To find the causative gene, the whole-exome sequencing was carried out.</p><p><b>RESULTS</b>Disease onset was from adolescence to adulthood, but the affected patients of the third generation presented an earlier onset and more severe clinical manifestations than the older generations. Clinical features were characterized as dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision. However, not every patient manifested all symptoms. Serum CK was mildly elevated and EMG indicated a myopathic pattern. Brain MRI showed cerebellum and brain stem mildly atrophy. Rimmed vacuoles and inclusion bodies were observed in muscle biopsy. The whole-exome sequencing was performed, but the causative gene has not been found.</p><p><b>CONCLUSIONS</b>We reported a novel autosomal dominant myopathy with rimmed vacuoles characterized by dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision, but the causative gene has not been found and needs further study.</p>

Primary Fallopian Tube Carcinoma: A Retrospective Clinical Analysis of 40 Patients / 中国肿瘤临床

Objective: To investigate the clinical features and survival factors of primary fallopian tube car-cinoma. Methods: We used Kaplan-Meier survival analysis, single factor analysis and multivariate analysis to evaluate the prognostic factors of 40 patients diagnosed with primary fallopian tube cancer. Results: The aver-age age of the patients was 51 years and all of them received surgery. There were 29 (72.5%) stage Ⅰ or Ⅱ patients, 11 stage Ⅲ or Ⅳ patients. Thirty-one (77.5%) patients were diagnosed with poorly differentiated tu-mors and 22 (55%) patients had serous adenocarcinoma. Thirty-seven patients received PAC/PC or TC che-motherapy after surgery. Six patients (15%) had recurrences within 23 to 56 months after surgery. The medi-an survival of Ⅰ～Ⅱ and Ⅲ～Ⅳ stage patients was 79 and 35 months, respectively. The total 5-year survival was 58% and 0 (P=0.005). Univariate and multivariate analysis showed that stage (Ⅰ～Ⅱ vs. Ⅲ-Ⅳ), grade (G_1+G_2 vs. G_3), residual disease after surgery (none, <1cm vs. >1cm) were significant factors affecting surviv-al. In accordance with the formula to calculate the half-life of CA125 and compare preoperative serum CA125 with the value at 3 weeks after surgery (T_(1/2)>3 week, T_(1/2)<3 week), the 5-year survival was 78% and 50%, re-spectively (P=0.036). Conclusion: Special attention should be paid to the joint screening of primary fallopian tube cancer in clinical practice in order to avoid misdiagnosis. The consecutive measurements of serum CA-125 level may have significant value as a prognostic indicator for patient survival.

Knockout of the hprK gene in B. subtilis CcpA mutant and its influence on riboflavin fermentation / 生物工程学报

In Bacillus subtilis , raising the amount of carbon catabolite in vivo would lead to carbon catabolite repression (CCR) and restrain the absorption of glucose. By deleting CcpA the CCR effect could be relieved, but the absorption of glucose remains restrained. The phosphoenol-pyruvate-sugar phosphotransferase system (PTS) is the main glucose transportation system in B. subtilis. HPr protein together with HprK/P participate in the glucose transportation. The HPr protein is phosphorylated at His-15 forming HPr-His-15-P transferring phosphate group from HPr to E II . While HprK/P phosphorylate HPr at Ser-46 forming HPr-Ser-46-P. HPr-Ser-46-P cannot participate in the transportation of glucose. The Knockout of ccpA gene increases the amount of fructose 1,6-bisphosphate(FBP) in vivo. And FBP could activate HPr kinase. So when CcpA is deleted, most part of the HPr will be phosphorylated at Ser-46. Absorpton of glucose is blocked. In this study, by disruption of hprk gene, the obtained B. subtilisZHc/pMX45 reaches the peak riboflavin production of 4.374mg/mL at the optimum glucose concentration of 10%, 19.2% higher than that of B. subtilis24 A1/pMX45 at the optimum glucose concentration of 8%.

Excess Inorganic Salt and Glutamine Repress Riboflavin Fermentation of Recombinant Bacillus subtilis / 微生物学通报

In the riboflavin fermentation by recombinant Bacillus subtilis 24/pMX45,The yeast powder facilitate riboflavin biosynthesis and the yeast extract have negative effect. It was found that the concentrations of inorganic ions and the amino acids in yeast extract were much higher than that of the yeast powder. The inorganic ions and the amino acids were respectively added to the medium while yeast powder was used as base nitrogen source. The fermentation results show that excess inorganic ions and glutamine have negative effect on riboflavin biosynthesis. The yeast extract restrained riboflavin biosynthesis for it contains much glutamic acid.